Research in this laboratory has been directed toward gaining further understanding of the molecular mechanisms by which the steroid sex hormones produce their myriad effects in their target tissues. Evidence from several laboratories using several kinds of test systems indicates that the synthesis of new species of RNA or the increased synthesis of several kinds of RNA follows the administration of the steroid. Some of the many kinds of RNA produced in increased amounts following hormone administration is messenger RNA which provides biological information for the synthesis of specific enzymes. The RNA isolated from the target tissue which is bound to polyuridylic acid separose columns (and subsequently eluted) will stimulate growth, protein synthesis, and the production of specific enzymes when introduced into the control tissue. The target tissues of steroid hormones are characterized by the presence of specific protein receptors which bind and accumulate the steroid, transferring it into the cell nucleus. There the steroid receptor complex interacts with chromatin and results in increased RNA synthesis. We have shown that the biological activity resides in RNA that is bound to polyuridylic acid sepharose columns and presumably has the polyadenylic acid tail at the 3' hydroxy end. The RNA not bound to these affinity columns is without effect when instilled. Using our two systems, the response of the uterus to estrogen and the response of the seminal vesicle or prostate to androgen, we will attempt to answer the following questions: What are the chemical and biological characteristics of the hormone-induced, biologically active, presumably poly(A)-rich RNA? How does the interaction of the hormone receptor complex with chromatin affect genetic read-out and produce this biologically active RNA? Why does a specific hormone affect the genetic mechanism of certain cells but not others in the same animal? Can this hormone-induced, biologically active RNA be transcribed in the cell-free system? Can other exogenous RNAs such as the avidin or ovalbumin messenger RNAs of the chick oviduct be read out in the uterine system? Answers to these questions should increase our understanding of molecular endocrinology and might aid in designing new therapeutic approaches to the design of contraceptives.